The purpose of this Funding Opportunity Announcement (FOA)
is to support innovative research projects designed to solve specific
problems and paradoxes in cancer research identified by the NCI Provocative
Questions initiative. These problems and paradoxes phrased as questions are
not intended to represent the full range of NCI's priorities in cancer
research. Rather, they are meant to challenge cancer researchers to think
about and elucidate specific problems in key areas of cancer research that
are deemed important but have not received sufficient attention.

Some of these "Provocative Questions" (PQs) stem
from intriguing but older, neglected observations that have never been
adequately explored. Other PQs are built on more recent findings that are
perplexing or paradoxical, revealing important gaps in current knowledge.
Finally, some PQs reflect problems that traditionally have been thought to be
intractable but that now may be open to investigations using new strategies
and recent technical advances.

In the second issuance in 2012, there were eight PQs FOAs,
each covering a subset of identified PQs and utilizing the R01 and R21
funding mechanisms. The current reissuance of the PQ Program involves
an updated set of 20 PQs. In order to facilitate the peer review
process, the new/updated PQs have been divided into five groups related by
themes resulting in five R01 FOAs and five R21 FOAs.

PQs in each Group are thematically related. However, the
order of the groups and numbering of questions within a group are essentially
arbitrary and should not be construed to indicate any order of priority.

This FOA (RFA-CA-13-021),
using the R21 exploratory/developmental funding mechanism, solicits
applications for PQs in Group C. The companion FOA for PQs in Group C, using
the R01 funding mechanism, is RFA-CA-13-020.
PQs in this group challenge investigators to seek answers to specific
unsolved problems generally related to the development or refinement of
methods to detect or diagnose tumors and highlight our still nascent
knowledge of the stages of tumor development as they relate to determining
which tumors are most likely to lead to more aggressive states.

Each research project proposed in response to this FOA
must be focused on solving one particular research problem defined by one
specific PQ selected from the list in Group C. Projects proposed to address
specific PQs may use strategies that incorporate ideas and approaches from
multiple disciplines, as appropriate. Transdisciplinary projects are
encouraged as long as they serve the scientific focus of the specific PQ chosen.

January 15, 2014 and June 20, 2014, by 5:00 PM local time
of applicant organization.

Applicants are encouraged to apply early to allow adequate
time to make any corrections to errors found in the application during the
submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

April-May 2014 and October-November 2014

Advisory Council Review

August 2014 and January 2015

Earliest Start Date

September 2014 and March 2015

Expiration Date

June 21, 2014

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed to do otherwise (in
this FOA or in a Notice from the NIH
Guide for Grants and Contracts). Conformance to all requirements (both
in the Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

The purpose of this Funding Opportunity Announcement (FOA)
is to support new research projects designed to use sound and innovative
strategies to solve specific problems and paradoxes in cancer research
identified by the National Cancer Institute (NCI) as the NCI’s Provocative
Questions (PQs).

This program covers five R01 FOAs and five parallel R21
FOAs. All FOAs for each mechanism are of identical format and general
requirements, differing only in specific PQs covered. This FOA solicits
applications for smaller, experimental/developmental research projects in
response to PQs in Group C using the NIH R21 funding mechanism. The companion
FOA, RFA-CA-13-020,
is a parallel announcement for larger, well-developed projects in response to
PQs in Group C using the NIH R01 mechanism.

To
be responsive to this FOA, each application must specifically address a
particular scientific problem identified as one of the PQs in Group C listed in
this FOA.

Background

The objective of the Provocative Questions Initiative is to
stimulate specific areas of cancer research that are understudied, neglected,
paradoxical, or have been difficult to address in the past. Both of the
previous issuances of PQs FOAs in 2011 and 2012 had been preceded by several
NCI-sponsored workshops to identify, articulate, and prioritize particularly
compelling but understudied problems in cancer research to create a list of
PQs. Following the two FOAs in 2011, eight FOAs were issued in 2012, utilizing the
R01 and R21 funding mechanisms.

For the current issuance of the PQ Program, the second list
of PQs is now updated to a set of 20 PQs. Some of these 20 PQs are new whereas
others are refocused relative to the prior lists. In order to facilitate
the peer review process, the new/updated PQs have been divided into five groups
(related by PQ themes), resulting in five R01 FOAs and five R21 FOAs.

Like the second set, these updated PQs also represent
diverse fields relevant to cancer research, but all are framed to inspire
interested scientists to conceive new approaches and/or feasible solutions.
These PQs are not intended to represent the full range of NCI's priorities in
cancer research. Rather, they are meant to challenge cancer researchers to think
about and elucidate specific problems in key areas of cancer research that are
deemed important but have not received sufficient attention.

The
Nature of Scientific Problems Underlying PQs

Regardless of topical area, most scientific problems underlying
the corresponding PQs fall into one of three broad types:

Ignored or neglected cancer-relevant problems that are brought
back into focus. These problems typically relate to intriguing older
observations or unresolved issues, for which satisfactory, rigorous research
answers may open up qualitatively new research avenues and/or result in
substantial progress in a given area.

More recent findings that are perplexing or paradoxical,
revealing important gaps in current knowledge. Research answers to these
problems are expected to have exceptionally high potential to re-shape current
key conception and paradigms about cancer.

Problems of recognized high importance that used to be
particularly difficult to explore but became open to investigations because of
recent scientific discoveries and technical advances.

List of PQs for this FOA: Group C

Each
application must address one and only one specific PQ from Group C, exactly as
defined in this FOA.

PQC1: (Rewritten for 2013) What properties of pre-cancerous
lesions or their microenvironment predict the likelihood of progression to
malignant disease?

PQC2: (Retained from 2012) What molecular or cellular events
establish tumor dormancy after treatment and what leads to recurrence?

PQC3: (New for 2013) How do variations in tumor-associated
immune responses among patients from distinct well-defined populations, such as
various racial/ethnic or age groups, contribute to differences in cancer
outcomes?

PQC4: (New for 2013) What in vivo imaging methods can be
developed to portray the "cytotype" of a tumor — defined as the
identity, quantity, and location of each of the different cell types that make
up a tumor and its microenvironment?

Specific Requirements

Scientific
Scope. The collective scientific scope of this FOA is defined by
the list of PQs in Group C. These PQs define research areas appropriate for
this FOA. They should NOT be construed as examples of specific topics. The
scientific scope of each individual application must clearly and distinctly
correspond to one (and only one) of the PQs listed above. Within an area
defined by a given PQ, applicants may propose and pursue any topic they deem
relevant as a "research answer" to that PQ. It is important, however,
that applicants visit the Provocative Questions web site (http://provocativequestions.nci.nih.gov/)
for additional information for each PQ pertaining to context, background,
feasibility, and expectations of needs to be accomplished for a successful
solving of these problems.

Applicants
who fail to choose a specific PQ from this list, address more than one PQ
within a single application, and/or re-write the PQ will have their
applications assessed as non-responsive. Non-responsive applications will not
be reviewed.

Applicants wishing to address more than one of the PQs may
still do so by submitting separate applications.

Individual
Goals. Within the research area defined by a specific PQ chosen,
the overarching goal of the proposed research project must be an attempt to
provide definitive, comprehensive, and thorough research answers to the problem
or portions of the problem presented by that question. The proposed research
solutions are expected to be creative and highly original with a high potential
for transformative impact on current concepts and paradigms in cancer research.

Within this general requirement, specific topics for the
proposed investigations, strategies, priority directions, and other details of
study design and execution are left to the discretion, originality, and
creativity of the applicants. The creativity and originality (combined with
scientific rigor) are particularly important, given that the areas identified
by the individual PQs are, generally, understudied. Therefore, the applicants
have the full freedom to identify the most promising direction(s) to address
the selected PQ, formulate Specific Aims, choose optimal experimental
approaches, and adapt appropriate specific benchmarks as measures of
accomplishing the overarching goal of the project. It is important that these
specific benchmarks will be in line with “Implications of Success” identified
for each of the PQs on the Provocative Questions website (http://provocativequestions.nci.nih.gov/).

Original
Rigorous Concepts versus Preliminary Data. In general, the R21
funding mechanism is used for pilot, exploratory research projects. For such
projects, preliminary data are not required, although may be included if
available. It is realized that for the areas of the PQs, there could be gaps in
background information and original preliminary data may be particularly scarce
or hard to get beforehand. The intention of this FOA is, by definition, to
exploit understudied areas. Therefore, the emphasis of this R21 FOA is on
concepts to be explored, i.e. the power of ideas behind the proposed research.
These concepts and ideas must be original but also rigorous in terms of integrating
to the best extent possible the available incomplete information for a given
area from various sources. These requirements are similar to those for the
companion R01 FOA (RFA-CA-13-020),
except that the scope of R21 projects is expected be narrower and in some cases
the projects may be based on more speculative, high-risk concepts.

Note: Research projects originally conceived as conventional
investigator-initiated projects and applications for continuation of such
projects are not likely to be viewed favorably in light of the priorities of
the PQ FOAs.

Required for Responsiveness

All applications submitted in response to this FOA are
expected to pose an original high impact hypothesis (that may be risky) but
also a solid research plan to validate the assumptions and test the hypothesis.

Therefore, all applications must contain a “Challenge Statement” (to be included under Research Strategy Section, see Section IV. Application and Submission
Information of this FOA for details). Applications without a Challenge Statement will be considered
non-responsive. Non responsive applications will not be reviewed. The Challenge Statement must convincingly address the following aspects:

Original Hypothesis;

Transformative Potential;

Innovative Approach;

Testable Conceptual Assumptions; and

Benchmarks for Hypothesis Validation.

All
application titles must begin with the PQ number on which the application is
based (insert number in parenthesis at the beginning of the title).

Not Responsive

The following types of projects are not appropriate for this
FOA and applications proposing such projects will not be reviewed:

Applications that fail to provide specific, convincing, and
properly organized/structured information (see above) that reviewers can use to
assess whether the proposed project truly goes beyond widely accepted concepts,
uses novel approaches, and promises substantially more significant outcomes
than incremental expansion of the current knowledge.

Section
II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or
both to an eligible entity to carry out an approved project or activity.

Application Types Allowed

New

The OER
Glossary and the SF424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations
and the submission of a sufficient number of meritorious applications.

For the group of PQs covered by this FOA (Group C), the
NCI intends to fund approximately three R21 awards per due date,
corresponding to a total of up to $0.5-1 million, for the first submission
round (2014) and a similar amount for the second (2015). Future year amounts
will depend on annual appropriations.

Award Budget

The combined budget for direct costs for the two year
project period may not exceed $275,000. No more than $200,000 may be
requested in any single year. Application budgets must reflect the actual
needs of the proposed project.

Award Project Period

The total project period may not exceed 2 years.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete and maintain the
following registrations as described in the SF 424 (R&R) Application Guide
to be eligible to apply for or receive an award. All registrations must be
completed prior to the application being submitted. Registration can take 6
weeks or more, so applicants should begin the registration process as soon as
possible. The NIH
Policy on Late Submission of Grant Applications states that failure to
complete registrations in advance of a due date is not a valid reason for a
late submission.

Dun and Bradstreet
Universal Numbering System (DUNS) - All registrations require that
applicants be issued a DUNS number. After obtaining a DUNS number, applicants
can begin both SAM and eRA Commons registrations. The same DUNS number must be
used for all registrations, as well as on the grant application.

System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least
annually. The renewal process may require as much time as the
initial registration. SAM registration includes the assignment of a Commercial
and Government Entity (CAGE) Code for domestic organizations which have not
already been assigned a CAGE Code.

eRA Commons - Applicants
must have an active DUNS number and SAM registration in order to complete the
eRA Commons registration. Organizations can register with the eRA Commons as
they are working through their SAM or Grants.gov registration. eRA Commons
requires organizations to identify at least one Signing Official (SO) and at
least one Program Director/Principal Investigator (PD/PI) account in order to
submit an application.

Grants.gov – Applicants
must have an active DUNS number and SAM registration in order to complete the
Grants.gov registration.

Program
Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account and should
work with their organizational officials to either create a new account or to
affiliate an existing account with the applicant organization’s eRA Commons
account. If the PD/PI is also the organizational Signing Official, they must
have two distinct eRA Commons accounts, one for each role. Obtaining an eRA
Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application that is essentially the
same as one already reviewed within the past thirty-seven months (as described
in the NIH
Grants Policy Statement), except for submission:

To an RFA of an application that was submitted previously as an
investigator-initiated application but not paid;

Of an investigator-initiated application that was originally
submitted to an RFA but not paid; or

Of an application with a changed grant activity code.

Section
IV. Application and Submission Information

1. Requesting an Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and
Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

Descriptive title of proposed research - include the PQ number being
addressed at the beginning of the title (in parenthesis);

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

Required and Optional Components

The forms package associated with this FOA includes all
applicable components, required and optional. Please note that some components
marked optional in the application package are required for submission of
applications for this FOA. Follow all instructions in the SF424 (R&R)
Application Guide to ensure you complete all appropriate “optional” components.

Instructions for Application Submission

The following section supplements the instructions found in
the SF424 (R&R) Application Guide and should be used for preparing an
application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide
must be followed

Descriptive
Title of Applicant’s Project: All application titles must begin
with the PQ number on which the application is based (insert PQ number at the
beginning of the title in parenthesis).

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide
must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide
must be followed.

Modular or R&R Budget

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide
must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Specific
Aims: This section must address the expected overall impact of
the project outcomes in terms of breadth and magnitude on cancer research.

Research
Strategy: this section must contain (place at the beginning of the section and within the
standard page limits) the following elements:

Provocative
Question (PQ) Choice. Identify one (and only one) specific PQ from
Group C that is being addressed in the proposed project and briefly describe
how you propose to provide an answer to the PQ selected.

Challenge
Statement. The Challenge Statement must address briefly (up to 1
page or less) the following:

Original
Hypothesis. Clearly state the hypothesis addressing the selected
PQ.

Transformative
Potential. Justify why the stated hypothesis would be
transformative if validated. Why is testing the proposed concept/hypothesis
and/or solving the problem important for the field defined by that particular
PQ?

Innovative
Approaches. Comparing to similar studies, explain why the proposed
hypothesis and/or approach are radically different and innovative. What aspects
make the proposed approach novel, different, and/or better from previous
attempts?

Testable
Conceptual Assumptions. State specific, testable assumptions that
underlie the stated hypothesis; and

Benchmarks
for Hypothesis Validation. What will be the main, rigorous measures
to test the assumptions and then demonstrate the validity of the hypothesis?

Resource
Sharing Plan: Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs
requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all
instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions
for completing Planned Enrollment Reports as described in the SF424 (R&R)
Application Guide.

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions
for completing Cumulative Inclusion Enrollment Report as described in the SF424
(R&R) Application Guide.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies
described in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications
before the due date to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants
across all Federal agencies). Applicants must then complete the submission process by tracking the
status of the application in the eRA Commons, NIH’s electronic system for grants
administration. NIH and Grants.gov systems check the application against many
of the application instructions upon submission. Errors must be corrected and a
changed/corrected application must be submitted to Grants.gov on or before the application
due date. If a Changed/Corrected application is submitted after the deadline,
the application will be considered late.

Applicants
are responsible for viewing their application before the due date in the eRA
Commons to ensure accurate and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the
SF424(R&R) Application Package. Failure to register in the Commons
and to include a valid PD/PI Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH. See Section III of this FOA for information on
registration requirements.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the System for Award Management. Additional information may be
found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH and for responsiveness by
the National Cancer Institute, NIH. Applications that are incomplete and/or
non-responsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-13-030.

Section
V. Application Review Information

1. Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement, note the following:

It is essential that research projects proposed in response
to this FOA meet the expectations in terms of exceptional creativity and
originality in addressing the selected PQ. To be viewed as having potential
high impact, the proposed research projects, as designed, must be likely to
yield far- or broad-reaching advances in the understanding of the research
problem defined by the selected PQ. Thus, potential impact of the applications
will be judged in large part on the power of the ideas behind the proposed
research.

The R21 exploratory/developmental grant supports
investigation of novel scientific ideas or new model systems, tools, or
technologies that have the potential for significant impact on biomedical or
biobehavioral research. A R21 grant application need not have extensive
background material or preliminary information. Accordingly, reviewers will
focus their evaluation on the conceptual framework, the level of innovation,
and the potential to significantly advance our knowledge or understanding.
Appropriate justification for the proposed work can be provided through
literature citations, data from other sources, or, when available, from
investigator-generated data. Preliminary data are not required for R21
applications; however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact score to reflect
their assessment of the likelihood for the project to exert a sustained,
powerful influence on the research field(s) involved, in consideration of the
following review criteria and additional review criteria (as applicable for the
project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Specific
to this FOA: How convincing and strong are arguments (including
those summarized in the Challenge Statement) that the proposed research project
will have profoundly more significant outcomes than incremental expansion of
the current knowledge? To what extent is this research project, as designed,
likely to yield far- or broad-reaching advances in our understanding for the
selected PQ?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD/PI, do the investigators have complementary
and integrated expertise; are their leadership approach, governance and
organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Specific
to this FOA: Does the proposed project address the selected PQ
in a new and fresh way? Does it provide opportunity for novel findings that
would be informative as answers for the selected PQ? For high risk projects, is
the potential for benefit justifiably high? In cases where the proposed project
is an extension of ongoing work, does it address truly original concepts and/or
research directions not covered by the ongoing work in a creative, innovative
way rather than simply taking the next logical step?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Specific
to this FOA: Is the experimental design optimal to ensure
generation of important information for the selected PQ? If negative results
are obtained, how likely is it that these results will be informative for our
understanding of the selected PQ? Do the applicants propose a conceptually
original and rigorous strategy to solve the problem defined by the selected PQ?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Specific
to this FOA: Are there any extraordinary aspects and/or
resources that provide novel or enhanced opportunities to investigate the
selected PQ in a way that would not be possible elsewhere even in generally
excellent scientific environments? For example, are there any unique, newly
developed/acquired technical capabilities (without which the project could not
be proposed) that are not available anywhere else?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact score, but will not give
separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Guidelines
for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Guidelines
for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the NCI, in
accordance with NIH peer
review policy and procedures, using the stated review
criteria. Assignment to a Scientific Review Group will be shown in the eRA
Commons.

As part of the scientific peer review, all applications:

Will undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit will be discussed and
assigned an overall impact/priority score.

Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in
response to this FOA.

Applications will be assigned to the NCI. Applications will
compete for available funds with all other recommended applications submitted
in response to this FOA. Following initial peer review, recommended applications
will receive a second level of review by the National Cancer Advisory Board. The
following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the
PD/PI will be able to access his or her Summary Statement (written critique)
via the eRA
Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

When multiple years are involved, awardees will be required
to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR)
and financial statements as required in the NIH
Grants Policy Statement.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and
405 of the Public Health Service Act as amended (42 USC 241 and 284) and under
Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.